Spatial multi-omics landscape of colorectal cancer macro- and micrometastases

Integrated spatial transcriptomic, genomic, and proteomic profiling of colorectal cancer metastases reveals early clonal divergence, stem-like cellular features, and immunosuppressive microenvironments characterized by T cell exhaustion already present at the micrometastasis stage. The study identifies a colorectal liver micrometastasis-specific six-gene signature (CLiMi) that correlates with minimal residual disease status, disease-free survival, and chemotherapy resistance. These findings provide a spatially resolved molecular atlas of metastatic progression and offer a clinically actionable biomarker panel for detecting occult disease and predicting treatment response.